scholarly journals Inflammation in rats born to mothers treated with dexamethasone 15cH during pregnancy: an immunohistochemical study

2021 ◽  
Vol 10 (35) ◽  
pp. 70-70
Author(s):  
Thayná Neves Cardoso ◽  
Leoni Villano Bonamin
Keyword(s):  
Mast Cell ◽  
Adhesion Molecules ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Mast Cell Degranulation ◽  
Polymorphonuclear Cells ◽  
Cellular Events ◽  
Detailed Assessment ◽  
Hematoxylin Eosin ◽  
Arteriolar Diameter

In previous studies, we observed that rats born to mothers treated with dexamethasone 15CH (10-33M) had a higher level of mast cell degranulation and greater arteriolar dilation after the exposure of an inflammatory stimulus, suggesting the possibility of vertical transmission of the effects of ultra-diluted substances between mother and offspring. In this study, a more detailed assessment of the cellular events in acute inflammation was made using techniques of immunohistochemistry. The identification of adhesion molecules expression was made by the markers: anti-CD54 (ICAM-1) and anti-CD18 (β2-Integrin). The identification of inflammatory cells was performed by the markers anti-MAC387 (mononuclear cells) and anti-CD163 (active macrophages). Polymorphonuclear cells were identified by hematoxylin-eosin staining. The number of labeled cells per field was recorded, except for the anti-CD54 marker, whose intensity of staining on the endothelial cells was defined by scores assigned by two independent observers. The results point toward to an up regulation of the whole inflammatory process in rats born to mothers treated with dexamethasone 15CH during pregnancy. This conclusion is justified by the following statistically significant (p≤0.05) findings: a) bigger mast cell degranulation and increased of arteriolar diameter; b) increased migration of polymorphonuclear cells in relation to the mononuclear cells; c) earlier expression of CD163 in monocytes, d) higher level of adhesion molecules expression.

scholarly journals Il6/Sil6R Regulates Tnfα-Inflammatory Response In Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα or IL6 and sIL6R for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cicloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assesed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results IL6/sIL6R stimulation of TNFα treated SF cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals Concurrent helminthosis engendered gastroenteritis in a leopard Panthera pardus

2019 ◽  
Vol 56 (4) ◽  
pp. 323-328
Author(s):  
R. Kumar ◽  
A. D. Moudgil ◽  
A. Sharma ◽  
R. Sharma ◽  
R. Masand ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Toxocara Canis ◽  
Intestinal Content ◽  
Detailed Examination ◽  
Pathological Examination ◽  
Polymorphonuclear Cells ◽  
Panthera Pardus ◽  
Parasitic Gastroenteritis ◽  
Present Case Study

SummaryThe necropsy of a leopard (Panthera pardus), succumbed to a chronic ailment exhibited a mixed parasitic gastroenteritis. Gross internal examination of carcass revealed the presence of round and tapeworms in the stomach and intestines with diffuse catarrhal and hemorrhagic gastroenteritis. The detailed examination of the intestinal content revealed the presence of Toxocara canis and Spirometra species eggs. Also, the gross morphological investigation of round and tapeworms approved the presence of both species. Histo-pathological examination showed sloughing of intestinal epithelium, hemorrhages, and ulcerative areas with the infiltration of polymorphonuclear cells admixed with mononuclear cells. Lungs revealed the accumulation of eosinophilic edematous fl uid in the alveolar spaces along with inflammatory cells. These parasites are pathogenic to precious wild felids and often pose a threat of zoonotic transmission due to spill-over infections. The present case study is an attempt to put on record a case of parasitic gastroenteritis in a captive leopard.

Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury

2006 ◽  
Vol 290 (6) ◽  
pp. L1059-L1068 ◽  
Author(s):  
Naoki Miyao ◽  
Yukio Suzuki ◽  
Kei Takeshita ◽  
Hiroyasu Kudo ◽  
Makoto Ishii ◽  
...  
Keyword(s):  
Lung Injury ◽  
Fluorescence Microscopy ◽  
Adhesion Molecules ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Laser Fluorescence ◽  
Confocal Laser ◽  
Polymorphonuclear Cells ◽  
Ventilator Induced Lung Injury ◽  
Endothelial Adhesion Molecules

Although the endothelial expression of various adhesion molecules substantially differs between pulmonary microvessels, their importance for neutrophil and lymphocyte sequestration in ventilator-induced lung injury (VILI) has not been systematically analyzed. We investigated the kinetics of polymorphonuclear cells (PMN) and mononuclear cells (MN) in the acinar microcirculation of the isolated rat lung with VILI by real-time confocal laser fluorescence microscopy, with or without inhibition of ICAM-1, VCAM-1, or P-selectin by monoclonal antibodies (MAb). Adhesion molecules in each microvessel were estimated by intravital fluorescence microscopy or immunohistochemical staining. In high tidal volume-ventilated lungs, 1) ICAM-1, VCAM-1, and P-selectin were differently upregulated in venules, arterioles, and capillaries; 2) venular PMN rolling was improved by inhibition of ICAM-1, VCAM-1, or P-selectin, whereas arteriolar PMN rolling was improved by ICAM-1 or VCAM-1 inhibition; 3) capillary PMN entrapment was ameliorated only by anti-ICAM-1 MAb; and 4) MN rolling in venules and arterioles and MN entrapment in capillaries were improved by ICAM-1 and VCAM-1 inhibition. In conclusion, the contribution of endothelial adhesion molecules to abnormal leukocyte behavior in VILI-injured microcirculation is microvessel and leukocyte specific. ICAM-1- and VCAM-1-dependent, but P-selectin-independent, arteriolar PMN rolling, which is expected to reflect the initial stage of tissue injury, should be taken as a phenomenon unique to ventilator-associated lung injury.

scholarly journals Primary demyelination as a nonspecific consequence of a cell-mediated immune reaction.

1975 ◽  
Vol 141 (2) ◽  
pp. 346-359 ◽  
Author(s):  
H M Wisniewski ◽  
B R Bloom
Keyword(s):  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Inflammatory Cells ◽  
Polymorphonuclear Cells ◽  
Inflammatory Reactions ◽  
Purified Protein Derivative ◽  
Primary Demyelination ◽  
Tissue Antigens ◽  
A Cell ◽  
Constant Feature

Primary demyelination occurs in a variety of human and experimental diseases known to be associated with the presence of inflammatory cells. However, the mechanism of demyelination remains unclear. The possibility that myelin can be damaged as a nonspecific consequence of a specific delayed type of hypersensitivity reaction directed at nonnervous tissue antigens was investigated. Guinea pigs were sensitized to tuberculin with Freund's complete adjuvant, and were challenged in the central and peripheral nervous system either with live or killed sonicated tubercle bacilli, Old Tuberculin, or tuberculin purified protein derivative (PPD). Local inflammatory reactions were invariably produced and primary demyelination was a constant feature of the lesions. The morphological picture was rather similar to that observed in human neurotuberculosis and early tuberculoid leprosy, and in experimental allergic encephalomyelitis and distemper encephalitis in animals. The infiltrates consisted predominantly of mononuclear cells with some polymorphonuclear cells as well. Vesicular disruption of the myelin sheath in the immediate vicinity of the inflammatory cells and stripping of the myelin lamellae by the histiocytes without axonal damage were the leading features of the lesion. The results indicate that cell-mediated immune reactions to a variety of nonbrain antigens could be responsible for a component of the demyelination seen in some inflammatory demyelinating conditions, and suggest that this system may serve as a useful model for studying the immunopathology of demyelinating disease.

scholarly journals A Phenotypic Screening Approach in Cord Blood–Derived Mast Cells to Identify Anti-Inflammatory Compounds

2013 ◽  
Vol 18 (10) ◽  
pp. 1223-1233 ◽  
Author(s):  
Rejbinder Kaur ◽  
Lisa A. Sloan ◽  
Andy D. Blanchard ◽  
Janet L. Smith ◽  
Ian Churcher ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cord Blood ◽  
Cell Biology ◽  
Serine Proteases ◽  
Mononuclear Cells ◽  
Allergic Inflammation ◽  
Mast Cell Degranulation ◽  
Prostaglandin D2 ◽  
Innovative Drug

Mast cells are unique hematopoietic cells that are richly distributed in the skin and mucosal surfaces of the respiratory and gastrointestinal tract. They play a key role in allergic inflammation by releasing a cocktail of granular constituents, including histamine, serine proteases, and various eicosanoids and cytokines. As such, a number of drugs target either inhibition of mast cell degranulation or the products of degranulation. To identify potential novel drugs and mechanisms in mast cell biology, assays were developed to identify inhibitors of mast cell degranulation and activation in a phenotypic screen. Due to the challenges associated with obtaining primary mast cells, cord blood–derived mononuclear cells were reproducibly differentiated to mast cells and assays developed to monitor tryptase release and prostaglandin D2 generation. The tryptase assay was particularly sensitive, requiring only 500 cells per data point, which permitted a set of approximately 12,000 compounds to be screened robustly and cost-effectively. Active compounds were tested for concomitant inhibition of prostaglandin D2 generation. This study demonstrates the robustness and effectiveness of this approach in the identification of potential novel compounds and mechanisms targeting mast cell–driven inflammation, to enable innovative drug discovery efforts to be prosecuted.

scholarly journals IL6/sIL6R regulates TNFα-inflammatory response in synovial fibroblasts through modulation of transcriptional and post-transcriptional mechanisms

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes ◽  
Two Factors

Abstract Introduction The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results The stimulation of SF with IL6/sIL6R and TNFα, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals IL6/sIL6R REGULATES TNFα-INFLAMMATORY RESPONSE IN SYNOVIAL FIBROBLASTS THROUGH MODULATION OF TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL MECHANISMS

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value <0.05 was considered statistically significant. Results: The stimulation of SF with IL6/sIL6R and TNFa, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals Induction of Mast-Cell Accumulation by Promutoxin, an Arg-49 PhospholipaseA2

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ji-Fu Wei ◽  
Xiao-Long Wei ◽  
Ya-Zhen Mo ◽  
Haiwei Yang ◽  
Shaoheng He
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Adhesion Molecules ◽  
Snake Venom ◽  
Platelet Activating Factor ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Cell Accumulation ◽  
Snake Venom Phospholipase ◽  
Main Component

Local inflammation is a prominent characteristic of snakebite wound, and snake-venom phospholipase A2s (PLA2s) are some of the main component that contribute to accumulation of inflammatory cells. However, the action of an R49 PLA2s, promutoxin fromProtobothrops mucrosquamatusvenom, on mast-cell accumulation has not been previously examined. Using a mouse peritoneal model, we found that promutoxin can induce approximately-6-fold increase in mast-cell accumulation, and the response lasts at least for 16 h. The promutoxin-induced mast cell accumulation was inhibited by cyproheptadine, terfenadine, and Ginkgolide B, indicating that histamine and platelet-activating factor (PAF) is likely to contribute to the mast-cells accumulation. Preinjection of antibodies against adhesion molecules ICAM-1, CD18, CD11a, and L-selectin showed that ICAM-1, and CD18, CD11a are key adhesion molecules of promutoxin-induced mast-cell accumulation. In conclusion, promutoxin can induce accumulation of mast cells, which may contribute to snake-venom wound.

scholarly journals IL6/sIL6R Regulates Tnfa-Inflammatory Response in Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF.Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value <0.05 was considered statistically significant.Results: The stimulation of SF with IL6/sIL6R and TNFa, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

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